Sickle cell disease, particularly in its homozygous form, is the result of a hereditary defect in hemoglobin biosynthesis which affects large numbers of the black population of the world and other located about the Mediterranean area. The hereditary molecular defect involves a single substitution of one valine residue for one glutamine residue in the beta chain of the hemoglobin molecule. This chemical substitution of a hydrophobic amino acid residue for a hydrophilic one makes the whole hemoglobin molecule slightly less water-soluble so that there is a tendency to crystallization of the molecule under two conditions: (1) when the pH of the extracellular body fluids decreases (i.e. acidosis with or without a high pCO.sub.2), or (2) when the concentration of water in these fluids decreases (i.e. dehydration). This it is found that sickle cell "crises" often start at night when there is a natural tendency to dehydration and metabolic acidosis during sleep (no oral hydration, continued formation of urine, tendency to hypoventilation, etc. ).
Crystallization of the hemoglobin in the red blood cells distorts their shape into sickle-like cells, and the latter tend to have difficulty in passage through capillaries. A large concentration of sickled cells in the circulation causes aggregation of the cells in capillaries, decreases capillary flow and oxygenation of tissues, increases peripheral vascular resistance and puts a load on the heart which may result in congestive heart failure. Cases vary in frequency and severity of such "crises", the frequency varying from weekly to monthly. Severe cases have short lives, with a particularly high mortality in young patients in many parts of the African continent. Pharmaceutical preparations so far used in an attempt to alter this sickling response of the red blood cells have in practically all instances proved as toxic or more toxic than the disease itself.
It has been known for some time that if the concentration of water surrounding sickled cells is increased either in vivo or in vitro, the sickling phenomenon can be reversed. Unfortunately, even with very large intravenous infusions of hypotonic fluids a state of sufficient hypo-osmolality is practically impossible to induce in patients, since their kidneys get rid of the water load as fast as it is given.